Mechanisms of nanosized titanium dioxide-induced testicular oxidative stress and apoptosis in male mice

BACKGROUND: Due to the increased application of titanium dioxide nanoparticles (TiO(2) NPs) in the food industry and daily life, their potential toxic effects in humans and animals have been investigated. However, very few studies have focused on testicular oxidative stress and/or apoptosis. METHODS: In order to understand the possible molecular mechanisms of testicular lesions following exposure to TiO(2) NPs, male mice were exposed to 2.5, 5, or 10 mg/kg body weight TiO(2) NPs for 90 consecutive days. Testicular oxidative stress and apoptosis were then evaluated, and the testicular mRNA expression of several genes and their proteins involved in oxidative stress and/or apoptosis was investigated. RESULTS: TiO(2) NPs entered Sertoli cells and caused severe testicular oxidative damage and/or apoptosis, accompanied by excessive production of reactive oxygen species and peroxidation of lipids, proteins and DNA as well as a significant reduction in antioxidant capacity. Furthermore, exposure to TiO(2) NPs resulted in the up-regulation of caspase-3, Nrbp2, and cytochrome c expression, and caused down-regulation of SOD, CAT, GPx, GST, GR, Cyp1b1, Car3, Bcl-2, Acaa2, and Axud1 expression in mouse testis. CONCLUSIONS: TiO(2) NPs entered Sertoli cells via the blood-testis barrier and were deposited in mouse seminiferous cord and/or Sertoli cells, causing oxidative damage and apoptosis.